Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease

Giovanni Mariscalco, Radoslaw Debiec, John A Elefteriades, Nilesh J Samani, Gavin J Murphy, Giovanni Mariscalco, Radoslaw Debiec, John A Elefteriades, Nilesh J Samani, Gavin J Murphy

Abstract

Background Nonsyndromic thoracic aortic diseases ( NS - TADs ) are often silent entities until they present as life-threatening emergencies. Despite familial inheritance being common, screening is not the current standard of care in NS - TAD s. We sought to determine the incidence of aortic diseases, the predictive accuracy of available screening tests, and the effectiveness of screening programs in relatives of patients affected by NS - TADs . Methods and Results A systematic literature search on PubMed/ MEDLINE , Embase, and the Cochrane Library was conducted from inception to the end of December 2017. The search was supplemented with the Online Mendelian Inheritance in Man database. A total of 53 studies were included, and a total of 2696 NS - TAD relatives were screened. Screening was genetic in 49% of studies, followed by imaging techniques in 11% and a combination of the 2 in 40%. Newly affected individuals were identified in 33%, 24%, and 15% of first-, second-, and third-degree relatives, respectively. Familial NS - TAD s were primarily attributed to single-gene mutations, expressed in an autosomal dominant pattern with incomplete penetrance. Specific gene mutations were observed in 25% of the screened families. Disease subtype and genetic mutations stratified patients with respect to age of presentation, aneurysmal location, and aortic diameter before dissection. Relatives of patients with sporadic NS - TAD s were also found to be affected. No studies evaluated the predictive accuracy of imaging or genetic screening tests, or the clinical or cost-effectiveness of an NS - TAD screening program. Conclusions First- and second-degree relatives of patients affected by both familial and sporadic NS - TAD s may benefit from personalized screening programs.

Keywords: aortic disease; genetic testing; mortality; screening.

Figures

Figure 1
Figure 1
Relatives screened in the studies included in the systematic review. Details for newly affected and not screened individuals are provided for first‐, second‐, and third‐degree relatives (FDRs, SDRs, and TDRs, respectively).
Figure 2
Figure 2
Schematic representation of genetic mutations with age and ascending aorta diameter at dissection. The widening of the circles/lines represents SD in terms of age and diameters. Data are obtained from studies included in the systematic review. No numerical data were available for patients affected by aortic dissection regarding the genes NOTCH1 and MFAP5, and patients with MAT2A mutation did not experience aortic dissections.1, 36, 43
Figure 3
Figure 3
Proposed flow chart for a dedicated screening program for relatives of patients affected by nonsyndromic diseases of the thoracic aorta based on the authors’ extensive literature review. The figure represents the best judgement of the authors. BAV indicates bicuspid aortic valve; CT, computed tomography; FDRs, first‐degree relatives; MRI, magnetic resonance imaging; NS‐TAD, nonsyndromic thoracic aortic disease; SDRs, second‐degree relatives; TTE, transthoracic echocardiogram.

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